Kappa receptor activation attenuates L-trans-pyrrolidine-2,4-dicarboxylic acid-evoked glutamate levels in the striatum.
The effects of local kappa receptor activation and blockade on extracellular striatal glutamate levels evoked by reverse microdialysis of L-trans-pyrrolidine-2,4-dicarboxylic acid (L-trans-PDC) were investigated. L-trans-PDC elevates extracellular glutamate levels in vivo by acting as a competitive substrate for plasma membrane excitatory amino acid transporters. The selective kappa-opioid receptor agonist U-69593 (1-100 nM) significantly attenuated L-trans-PDC-stimulated glutamate levels in a concentration-dependent manner. The selective kappa receptor antagonist nor-binaltorphimine (1-100 nM) reversed the U-69593-induced decrease in L-trans-PDC-evoked glutamate levels also in a concentration-dependent manner, indicating that the U-69593-induced reduction was mediated by kappa receptor activation. In addition, nor-binaltorphimine significantly elevated basal extracellular glutamate levels, implying that kappa receptors tonically regulate glutamate efflux in the striatum. Previous data from this laboratory have shown that L-trans-PDC-evoked extracellular glutamate levels are partially calcium-sensitive. The present study demonstrated that the inhibition of L-trans-PDC-evoked glutamate levels by reduced calcium perfusion was not altered by U-69593. Therefore, kappa receptors regulate the calcium-dependent component of L-trans-PDC-evoked extracellular glutamate levels in the striatum.
Rawls
S M
SM
Department of Anatomy and Cell Biology, East Carolina University School of Medicine, Greenville, North Carolina 27858-4354, USA.
McGinty
J F
JF
D000818:Animals; D044482:Benzeneacetamides; D002118:Calcium / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003998:Dicarboxylic Acids / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D017551:Microdialysis / Q000379:methods; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D010477:Perfusion / Q000379:methods; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*
D044482:Benzeneacetamides; D003998:Dicarboxylic Acids; D014179:Neurotransmitter Uptake Inhibitors; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D018698:Glutamic Acid; D009271:Naltrexone; C083486:pyrrolidine-2,4-dicarboxylic acid; C045444:U 69593; D002118:Calcium